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The World Health Organization recommends that programs include mortality and AMR monitoring. Niger is expanding the azithromycin MDA for child survival program nationwide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To establish program monitoring and leverage the infrastructure to evaluate other community health interventions, AVENIR II is designed as a cluster-randomized adaptive platform trial with monitoring and re-randomization every 2\u00a0years. The initial focus is to monitor under-5 mortality, AMR, implementation, and safety as the azithromycin program expands in Niger. All eligible primary health center catchment areas (Centre de Sant\u00e9 Int\u00e9gr\u00e9s, CSIs) will be included in biannual oral azithromycin MDA to children 1\u201359\u00a0months old. A subset will be randomized to delay MDA for the first 2\u00a0years, after which they will receive MDA. Another subset will then be randomized to stop MDA for the next 2\u00a0years. The proportion randomized to delay or stop will be determined using an adaptive algorithm including (1) results of prior azithromycin MDA mortality trials, (2) expert opinion on the appropriate ethical balance between delivering the program and monitoring AMR, and (3) statistical power to detect a programmatically relevant difference between arms. We anticipate 5\u201310% of CSIs will be randomized to delay or stop at each randomization. Mortality and AMR will be monitored at baseline and every 2\u00a0years. Implementation and safety outcomes will be monitored continuously. To enable ongoing monitoring while ensuring program access, CSIs receiving MDA will be re-randomized using the adaptive algorithm updated with new mortality results, and no CSI will go without MDA for more than 2\u00a0years. In this platform design, additional arms may be added or dropped based on information from other studies, updates to guidelines, or preferences of Niger policymakers, and other interventions may be evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The risk of AMR has led to caution in the implementation of azithromycin MDA. We present a design that enables continued rigorous evaluation of program impact on key outcomes, with flexibility to evaluate other interventions as well.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT06358872. Registered on April 2024.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-026-09561-2","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:18:13Z","timestamp":1771395493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Azithromycin mass drug administration to reduce child mortality in Niger (AVENIR II): a master protocol for a cluster-randomized adaptive platform trial to evaluate community-based health interventions"],"prefix":"10.1186","volume":"27","author":[{"given":"Ahmed M.","family":"Arzika","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdou","family":"Amza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sani","family":"Ousmane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramatou","family":"Maliki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Almou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser","family":"Galo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser","family":"Harouna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alio","family":"Mankara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bawa","family":"Aichatou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ousseini","family":"Boubacar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Lebas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Picariello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis C.","family":"Porco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy","family":"Doan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin F.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Lietman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran S.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"issue":"17","key":"9561_CR1","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1056\/NEJMoa1715474","volume":"378","author":"JD Keenan","year":"2018","unstructured":"Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, et al. 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The Comit\u00e9 National \u00c9thique pour la Recherche en Sant\u00e9 in Niger granted ethical approval before study activities began (DELIBERATION No. 14\/2024\/CNERS). Verbal informed consent will be obtained from the head of household for participation in the census and from caregiver\/guardians for treatment administration and outcome data collection, as is standard for studies of mass drug administration in this setting. Verbal consent will be obtained from regional, district, and community leaders before recruiting any participants into the study. Consent and refusals will be tracked in the data collection systems for each activity. There is no financial cost to the participant and there is no reimbursement for overall participation in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No data have been included in this study protocol. No details, images, or videos relating to individuals have been included. The authors will provide the verbal consent scripts used in this study upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"235"}}